Antibody therapeutics that bind JAG1

Abstract

There is disclosed compositions and methods relating to or derived from anti-JAG1 antibodies. More specifically, there is disclosed fully human antibodies that bind JAG1, JAG1-binding fragments and derivatives of such antibodies, and JAG1-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating or diagnosing subjects having JAG1 related disorders or conditions. There is also disclosed a method for treating JAG1-expressing tumors, including hepatocellular carcinomas and squamous carcinomas, and non-oncology diseases selected from the group consisting of rheumatoid arthritis, experimental lung injury, atherosclerosis, chronic liver disease induced by hepatitis C virus, ischemic myocardial injury and heart failure.

We claim: 
     
       1. An isolated anti-JAG1 fully human antibody of an IgG class that binds to a JAG1 epitope, said antibody comprising heavy/light chain variable domain amino acid sequences selected from the group consisting of: SEQ ID NO: 77/SEQ ID NO: 78, SEQ ID NO: 111/SEQ ID NO: 112, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 111/SEQ ID NO: 114, SEQ ID NO: 111/SEQ ID NO: 115, SEQ ID NO: 111/SEQ ID NO: 116, SEQ ID NO: 111/SEQ ID NO: 117, SEQ ID NO: 111/SEQ ID NO: 118, SEQ ID NO: 111/SEQ ID NO: 119, SEQ ID NO: 111/SEQ ID NO: 120, SEQ ID NO: 111/SEQ ID NO: 121, SEQ ID NO: 111/SEQ ID NO: 122, SEQ ID NO: 111/SEQ ID NO: 123, SEQ ID NO: 124/SEQ ID NO: 112, SEQ ID NO: 125/SEQ ID NO: 112, SEQ ID NO: 126/SEQ ID NO: 112, SEQ ID NO: 127/SEQ ID NO: 112, SEQ ID NO: 128/SEQ ID NO: 112, SEQ ID NO: 129/SEQ ID NO: 112, SEQ ID NO: 130/SEQ ID NO: 112, SEQ ID NO: 127/SEQ ID NO: 131, SEQ ID NO: 132/SEQ ID NO: 133, SEQ ID NO: 132/SEQ ID NO: 123, SEQ ID NO: 142/SEQ ID NO: 123, SEQ ID NO: 127/SEQ ID NO: 123, SEQ ID NO:132/SEQ ID NO: 134, SEQ ID NO: 135/SEQ ID NO: 133, SEQ ID NO: 132/SEQ ID NO: 136, SEQ ID NO: 132/SEQ ID NO: 137, SEQ ID NO: 132/SEQ ID NO: 138, SEQ ID NO: 139/SEQ ID NO: 123, SEQ ID NO: 139/SEQ ID NO: 140, and SEQ ID NO: 127/SEQ ID NO: 141. 
     
     
       2. The fully human antibody of  claim 1 , wherein the antibody has a K D  of at least 1×10 −6  M. 
     
     
       3. The fully human antibody of  claim 1 , wherein the antibody is a single chain antibody comprising a peptide linker connecting the heavy and light chain variable domains. 
     
     
       4. An anti-JAG1 fully human antibody Fab fragment, wherein the antibody Fab fragment comprises heavy/light chain variable domain amino acid sequences selected from the group consisting of: SEQ ID NO: 77/SEQ ID NO: 78, SEQ ID NO: 111/SEQ ID NO: 112, SEQ ID NO: 111, SEQ ID NO: 113, SEQ ID NO: 111/SEQ ID NO: 114, SEQ ID NO: 111/SEQ ID NO: 115, SEQ ID NO: 111/SEQ ID NO: 116, SEQ ID NO: 111/SEQ ID NO: 117, SEQ ID NO: 111/SEQ ID NO: 118, SEQ ID NO: 111/SEQ ID NO: 119, SEQ ID NO: 111/SEQ ID NO: 120, SEQ ID NO: 111/SEQ ID NO: 121, SEQ ID NO: 111/SEQ ID NO: 122, SEQ ID NO: 111/SEQ ID NO: 123, SEQ ID NO: 124/SEQ ID NO: 112, SEQ ID NO: 125/SEQ ID NO: 112, SEQ ID NO: 126/SEQ ID NO: 112, SEQ ID NO: 127/SEQ ID NO: 112, SEQ ID NO: 128/SEQ ID NO: 112, SEQ ID NO: 129/SEQ ID NO: 112, SEQ ID NO: 130/SEQ ID NO: 112, SEQ ID NO: 127/SEQ ID NO: 131, SEQ ID NO: 132/SEQ ID NO: 133, SEQ ID NO: 132/SEQ ID NO: 123, SEQ ID NO: 142/SEQ ID NO: 123, SEQ ID NO: 127/SEQ ID NO: 123, SEQ ID NO:132/SEQ ID NO: 134, SEQ ID NO: 135/SEQ ID NO: 133, SEQ ID NO: 132/SEQ ID NO: 136, SEQ ID NO: 132/SEQ ID NO: 137, SEQ ID NO: 132/SEQ ID NO: 138, SEQ ID NO: 139/SEQ ID NO: 123, SEQ ID NO: 139/SEQ ID NO: 140, and SEQ ID NO: 127/SEQ ID NO: 141. 
     
     
       5. The fully human antibody Fab fragment of  claim 4 , which has a K D  of at least 1×10 −6  M.